Aging and the Immune System: the Impact of Immunosenescence on Viral Infection, Immunity and Vaccine Immunogenicity

Abstract

Immunosenescence is characterized by a progressive deterioration of the immune system associated with aging. Multiple components of both innate and adaptive immune systems experience aging-related changes, such as alterations in the number of circulating monocytic and dendritic cells, reduced phagocytic activities of neutrophils, limited diversity in B/T cell repertoire, T cell exhaustion or inflation, and chronic production of inflammatory cytokines known as inflammaging. The elderly are less likely to benefit from vaccinations as preventative measures against infectious diseases due to the inability of the immune system to mount a successful defense. Therefore, aging is thought to decrease the efficacy and effectiveness of vaccines, suggesting aging-associated decline in the immunogenicity induced by vaccination. In this review, we discuss aging-associated changes in the innate and adaptive immunity and the impact of immunosenescence on viral infection and immunity. We further explore recent advances in strategies to enhance the immunogenicity of vaccines in the elderly. Better understanding of the molecular mechanisms underlying immunosenescence-related immune dysfunction will provide a crucial insight into the development of effective elderly-targeted vaccines and immunotherapies.

Keywords: Aging; Immunosenescence; Vaccines; Viral infections.

Figure 1. Multiple factors involved in aging. The diagram highlights multiple factors involved in aging; genomic instability, telomere attrition, epigenetic alterations, sarcopenia, changes in intracellular communication, cellular senescence, immunosenescence, and mitochondrial dysfunction.

Figure 2. The impact of immunosenescence on persistent viral infection and immunity. Aging leads to numerous changes in major components of both the innate and adaptive immune systems. In response to a viral infection, innate immune cells can trigger the activation of IFN pathways to clear the virus-infected cells. Age-associated defects in innate immune cells can lead to reduced IFN production. Persistent viral infection, such as CMV persistence, can have a profound effect on alterations in adaptive immunity, in particular, T cell composition and function. In the elderly, there are decreased numbers of naïve T cells, but increased numbers of senescent, inflationary, or exhausted T cells that are functionally inert or dormant.